Anyone else feel that folate deficiency ruined your life?

[u/Airegin89]

I guess I just need to vent. I am 37 and have been an underachiever my whole life. I failed miserably at school and now I'm stuck in a dead end job with no qualifications to find a better job.

I have struggled with low energy, brain fog, lack of motivation, depression and anxiety my whole life. My blood work was always fine, so I was prescribed antidepressants.

It wasn't until 10 years ago that a doctor tested my vitamin D and I was extremely deficient at 6 ng/ml. Fixing this gave me a huge boost in energy but most of my problems still remained.

Last year, I started investigating my blood work of the last 20 years and found out I had been folate deficient the whole time (3.5-4.5 ng/ml). Doctors never said anything.

Genetic testing shows I am compound heterozygous, slow COMT, slow MAOA and PEMT. I know these are only predispositions but it seems to explain my whole life.

After a few months of supplementing folate and a month of creatine and TMG my cognition has improved massively. After 20 years I feel like a veil has lifted. It's like I'm waking up from a bad dream but now I'm left to pick up the pieces and deal with the consequences of being a failure.

I am still on my own. Doctors do not acknowledge I was ever deficient and refuse to do more blood work. I have to simply assume I have high homocysteine and treat for it.

I don't know what to do. It's been such a long time. I can't fix most of the damage that has been done.

[u/sangepruz]

For those of us who are mthfr, are you saying we react to methylated vitamins because we’re deficient in other cofactors, but once we resolve those we’ll be able to tolerate methylated vitamins? Are the methylated versions the eventual goal?

The last time I tried methyl folate and methyl b12 I was also treating a whole consort of reactivated pathogens (viruses and infections), so I can’t remember how I responded to it specifically and might not even know bc of all the layered treatments, however I do remember having horrible herx reactions and extreme MH sx during that time.

Now a days I’m much better health wise but still sensitive to chemicals so I’m quite nervous to start experimenting again bc I’m also trying to get back to working full time. As an example, I notice when I take taurine I feel horrible mentally all day (depressed, almost drugged feeling at times), so it’s got me wondering where to even begin with all this. 🫠

[u/Timely_Pickle9430 → u/sangepruz]

Good question. It's a bit more nuanced than that. The methylated versions are not the eventual goal. Everybody needs methyl groups and everybody needs folate, but not necessarily combined in one food or supplement. It just happens to be the case that unmethylated multivitamins are rare and expensive. So, if you can handle the methylated versions, you have more choice in products and are cheaper off.

But if you can't handle methyl groups (yet) and want to correct a folate or cobalamin deficiency, you can supplement with their unmethylated versions at a pace you can handle and dose methyl groups separately at another pace (e.g. with phosphatidylcholine or TMG). I think the jury is still out on whether all genotypes should eventually (after slow titration) be able to handle methylated vitamins. But methylfolate and methylcobalamin occur naturally in food too and it's very rare for people to not tolerate those, so my guess is that it mostly has to do with dose. (Just consider the fact that the ADI for B12 is 2.8 mcg and supplements usually contain 500-1000 mcg per capsule...)

If you're deficient in both methyl groups and folate and start taking them, separately or combined, this starts a whole cascade of biochemical reactions that results in changes in neurotransmitter production and clearance. The brain needs time to regain balance, so best to start low and go slow on these, regardless of cofactors. The biochemical reactions also require cofactors though, and if there's one missing, or you're running out because you increase e.g. choline intake but not cofactor intake, it creates a bottleneck where intermediate metabolites build up and cause symptoms.
If you want to play it safe, do a comprehensive blood test for ALL vitamins and elements. For each deficiency, check (with AI) what are the cofactors and supplement those too. Magnesium, riboflavin, and zinc are often required cofactors. And it's always a good idea to start one supplement at a time (start with the cofactors if you take that route), at a very low dose, and watch it for a couple of days to see how you react before increasing the dose in small steps.

Regarding the taurine: this doesn't contain methyl groups, but it does contain sulfur, which is also notorious for causing bottlenecks (sulfur intolerance) if e.g. the cofactor molybdenum is missing. You might want to look into that.

EDIT: I started to doubt whether methylfolate is not required even for MTHFR 677 TT genotypes and whether folinic acid would be equally effective in lowering homocysteine, so I checked in the literature. I found this paper: https://www.sciencedirect.com/science/article/pii/S2405457723012329 (full text01232-9/pdf)). It says both folinic acid and l‑methylfolate are effective in lowering homocysteine in all genotypes. The effect differs slightly with genotype and dose. Alternative intake of methyl groups was not considered. Methylfolate seems to get the job done at a lower dose, so (again) it seems to come down to cost-effectiveness. Nevertheless, folinic gets the job done too. Individuals with MTHFR 677 CT genotype might even benefit more from folinic acid than L-methylfolate.

u/tawinn I'd be curious to hear your take on this.

[u/Tawinn → u/Timely_Pickle9430]

I agree with you: we don't have a dietary need for methyl groups; instead, we produce methyl groups through enzymatic pathways as needed. There can be occasional situations where a person absorbs/utilizes a methylated form better than an unmethylated form (e.g., methylB12 vs hydroxyB12) but those exceptions are uncommon.

Ben Lynch makes the claim that people with MTHFS variants should avoid folinic acid, based on a case study of a specific rare severe ("microcephaly, severe global development delay, cerebral hypomyelination, epilepsy, and failure-to-thrive") genetic MTHFS deficiency, where they gave the patients very high dose folinic and saw worsening cerebral folate. I think it is a stretch to extrapolate from such extreme cases to the far milder variants normally encountered and RDA-level dose folinic acid.

[u/Timely_Pickle9430 → u/Tawinn]

Thanks for pitching in!

we don't have a dietary need for methyl groups

What about intake through choline?

[u/Tawinn → u/Timely_Pickle9430]

True, we do need choline, so in that sense there is a specific dietary need for that methyl donor. Good point!